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Treatment adherence makes big impact in psychogenic nonepileptic seizures
HOUSTON – Patients with psychogenic nonepileptic seizures who stick with evidence-based treatment have significantly fewer seizures and have less associated disability than do those who don’t make it to therapy and psychiatry visits, a study showed.
Reporting preliminary data from 59 patients in a 123-patient study, Benjamin Tolchin, MD, and his colleagues said that patients who adhered to their treatment plans were significantly more likely to experience a reduction in seizure frequency of more than 50%, compared with nonadherent patients (P = .018). Treatment dropout was positively associated with having a prior psychogenic nonepileptic seizure (PNES) diagnosis and with having less concern about the illness.
These figures, he said, are consistent with what’s been reported in the PNES literature. Others have found that after diagnosis, 20%-30% of patients don’t attend their first appointment, although psychiatric treatment and therapy constitute evidence-based care that is effective in treating PNES.
Dr. Tolchin said previous studies have found that “over 71% of patients were found to have seizures and associated disability at the 4-year follow-up mark.”
In addition to tracking adherence, Dr. Tolchin and his coinvestigators attempted to identify risk factors for nonadherence among their patient cohort, all of whom had documented PNES. Study participants provided general demographic data, and investigators also gathered information about PNES event frequency; any prior diagnosis of PNES or other psychiatric comorbidities; history of physical, emotional, or sexual abuse; and health care resource utilization. Patients also were asked about their quality of life and time from symptom onset to receiving the PNES diagnosis.
Finally, patients filled out the Brief Illness Perception Questionnaire (BIPQ). This instrument measures various aspects of patients’ cognitive and emotional representations of illness, using a nine-item questionnaire. Higher scores indicate that the patient sees the illness as more concerning.
All patients were referred for both psychotherapy and four follow-up visits with a psychiatrist. The first psychiatric visit was to occur within 1-2 months after receiving the PNES diagnosis, with the next two visits occurring at 1.5- to 3-month intervals following the first visit. The final scheduled follow-up visit was to occur 6-9 months after the third visit.
Most patients (85%) were female and non-Hispanic white (77%), with a mean age of 38 years (range, 18-80). About one-third of patients were single, and another third were married. The remainder were evenly split between having a live-in partner and being separated or divorced, with just 2% being widowed.
By self-report, more than one-third of patients (37%) were on disability, and nearly one-quarter (24%) were unemployed. Just 18% were working full time; another 11% worked part time, and 8% were students.
The median weekly number of PNES episodes per patient was two, although reported events per week ranged from 0 to 350.
Psychiatric comorbidities were very frequent: 94% of patients reported some variety of psychiatric disorder. Depressive disorders were reported by 78% of patients, anxiety disorders by 61%, and posttraumatic stress disorder by 54%. Other commonly reported psychiatric diagnoses included panic disorder (40%), phobias (38%), and personality disorders (31%).
Almost a quarter of patients (23%) had attempted suicide in the past, and the same percentage reported a history of substance abuse. Patient reports of emotional (57%), physical (45%), and sexual (42%) abuse were also common.
Having a prior diagnosis of PNES was identified as a significant risk factor for dropping out of treatment (hazard ratio, 1.57; 95% confidence interval, 1.01-2.46; P = .046]. Patients with a higher concern for their illness, as evidenced by a higher BIPQ score, were less likely to drop out of treatment (HR, 0.77 for 10-point increment; 95% CI, 0.64-0.93; P = .008).
“Neurologists and behavioral health specialists need new interventions to improve adherence with treatment and prevent long-term disability,” Dr. Tolchin said.
The study, which won the Kaufman Honor for the highest-ranking abstract in the comorbidities topic category at the meeting, was supported by a practice research training fellowship from the American Academy of Neurology and the American Brain Foundation. Dr. Tolchin reported no other disclosures.
[email protected]
On Twitter @karioakes
HOUSTON – Patients with psychogenic nonepileptic seizures who stick with evidence-based treatment have significantly fewer seizures and have less associated disability than do those who don’t make it to therapy and psychiatry visits, a study showed.
Reporting preliminary data from 59 patients in a 123-patient study, Benjamin Tolchin, MD, and his colleagues said that patients who adhered to their treatment plans were significantly more likely to experience a reduction in seizure frequency of more than 50%, compared with nonadherent patients (P = .018). Treatment dropout was positively associated with having a prior psychogenic nonepileptic seizure (PNES) diagnosis and with having less concern about the illness.
These figures, he said, are consistent with what’s been reported in the PNES literature. Others have found that after diagnosis, 20%-30% of patients don’t attend their first appointment, although psychiatric treatment and therapy constitute evidence-based care that is effective in treating PNES.
Dr. Tolchin said previous studies have found that “over 71% of patients were found to have seizures and associated disability at the 4-year follow-up mark.”
In addition to tracking adherence, Dr. Tolchin and his coinvestigators attempted to identify risk factors for nonadherence among their patient cohort, all of whom had documented PNES. Study participants provided general demographic data, and investigators also gathered information about PNES event frequency; any prior diagnosis of PNES or other psychiatric comorbidities; history of physical, emotional, or sexual abuse; and health care resource utilization. Patients also were asked about their quality of life and time from symptom onset to receiving the PNES diagnosis.
Finally, patients filled out the Brief Illness Perception Questionnaire (BIPQ). This instrument measures various aspects of patients’ cognitive and emotional representations of illness, using a nine-item questionnaire. Higher scores indicate that the patient sees the illness as more concerning.
All patients were referred for both psychotherapy and four follow-up visits with a psychiatrist. The first psychiatric visit was to occur within 1-2 months after receiving the PNES diagnosis, with the next two visits occurring at 1.5- to 3-month intervals following the first visit. The final scheduled follow-up visit was to occur 6-9 months after the third visit.
Most patients (85%) were female and non-Hispanic white (77%), with a mean age of 38 years (range, 18-80). About one-third of patients were single, and another third were married. The remainder were evenly split between having a live-in partner and being separated or divorced, with just 2% being widowed.
By self-report, more than one-third of patients (37%) were on disability, and nearly one-quarter (24%) were unemployed. Just 18% were working full time; another 11% worked part time, and 8% were students.
The median weekly number of PNES episodes per patient was two, although reported events per week ranged from 0 to 350.
Psychiatric comorbidities were very frequent: 94% of patients reported some variety of psychiatric disorder. Depressive disorders were reported by 78% of patients, anxiety disorders by 61%, and posttraumatic stress disorder by 54%. Other commonly reported psychiatric diagnoses included panic disorder (40%), phobias (38%), and personality disorders (31%).
Almost a quarter of patients (23%) had attempted suicide in the past, and the same percentage reported a history of substance abuse. Patient reports of emotional (57%), physical (45%), and sexual (42%) abuse were also common.
Having a prior diagnosis of PNES was identified as a significant risk factor for dropping out of treatment (hazard ratio, 1.57; 95% confidence interval, 1.01-2.46; P = .046]. Patients with a higher concern for their illness, as evidenced by a higher BIPQ score, were less likely to drop out of treatment (HR, 0.77 for 10-point increment; 95% CI, 0.64-0.93; P = .008).
“Neurologists and behavioral health specialists need new interventions to improve adherence with treatment and prevent long-term disability,” Dr. Tolchin said.
The study, which won the Kaufman Honor for the highest-ranking abstract in the comorbidities topic category at the meeting, was supported by a practice research training fellowship from the American Academy of Neurology and the American Brain Foundation. Dr. Tolchin reported no other disclosures.
[email protected]
On Twitter @karioakes
HOUSTON – Patients with psychogenic nonepileptic seizures who stick with evidence-based treatment have significantly fewer seizures and have less associated disability than do those who don’t make it to therapy and psychiatry visits, a study showed.
Reporting preliminary data from 59 patients in a 123-patient study, Benjamin Tolchin, MD, and his colleagues said that patients who adhered to their treatment plans were significantly more likely to experience a reduction in seizure frequency of more than 50%, compared with nonadherent patients (P = .018). Treatment dropout was positively associated with having a prior psychogenic nonepileptic seizure (PNES) diagnosis and with having less concern about the illness.
These figures, he said, are consistent with what’s been reported in the PNES literature. Others have found that after diagnosis, 20%-30% of patients don’t attend their first appointment, although psychiatric treatment and therapy constitute evidence-based care that is effective in treating PNES.
Dr. Tolchin said previous studies have found that “over 71% of patients were found to have seizures and associated disability at the 4-year follow-up mark.”
In addition to tracking adherence, Dr. Tolchin and his coinvestigators attempted to identify risk factors for nonadherence among their patient cohort, all of whom had documented PNES. Study participants provided general demographic data, and investigators also gathered information about PNES event frequency; any prior diagnosis of PNES or other psychiatric comorbidities; history of physical, emotional, or sexual abuse; and health care resource utilization. Patients also were asked about their quality of life and time from symptom onset to receiving the PNES diagnosis.
Finally, patients filled out the Brief Illness Perception Questionnaire (BIPQ). This instrument measures various aspects of patients’ cognitive and emotional representations of illness, using a nine-item questionnaire. Higher scores indicate that the patient sees the illness as more concerning.
All patients were referred for both psychotherapy and four follow-up visits with a psychiatrist. The first psychiatric visit was to occur within 1-2 months after receiving the PNES diagnosis, with the next two visits occurring at 1.5- to 3-month intervals following the first visit. The final scheduled follow-up visit was to occur 6-9 months after the third visit.
Most patients (85%) were female and non-Hispanic white (77%), with a mean age of 38 years (range, 18-80). About one-third of patients were single, and another third were married. The remainder were evenly split between having a live-in partner and being separated or divorced, with just 2% being widowed.
By self-report, more than one-third of patients (37%) were on disability, and nearly one-quarter (24%) were unemployed. Just 18% were working full time; another 11% worked part time, and 8% were students.
The median weekly number of PNES episodes per patient was two, although reported events per week ranged from 0 to 350.
Psychiatric comorbidities were very frequent: 94% of patients reported some variety of psychiatric disorder. Depressive disorders were reported by 78% of patients, anxiety disorders by 61%, and posttraumatic stress disorder by 54%. Other commonly reported psychiatric diagnoses included panic disorder (40%), phobias (38%), and personality disorders (31%).
Almost a quarter of patients (23%) had attempted suicide in the past, and the same percentage reported a history of substance abuse. Patient reports of emotional (57%), physical (45%), and sexual (42%) abuse were also common.
Having a prior diagnosis of PNES was identified as a significant risk factor for dropping out of treatment (hazard ratio, 1.57; 95% confidence interval, 1.01-2.46; P = .046]. Patients with a higher concern for their illness, as evidenced by a higher BIPQ score, were less likely to drop out of treatment (HR, 0.77 for 10-point increment; 95% CI, 0.64-0.93; P = .008).
“Neurologists and behavioral health specialists need new interventions to improve adherence with treatment and prevent long-term disability,” Dr. Tolchin said.
The study, which won the Kaufman Honor for the highest-ranking abstract in the comorbidities topic category at the meeting, was supported by a practice research training fellowship from the American Academy of Neurology and the American Brain Foundation. Dr. Tolchin reported no other disclosures.
[email protected]
On Twitter @karioakes
AT AES 2016
Key clinical point:
Major finding: Adherent patients were more likely to reduce their seizures by half or more (P = .018).
Data source: A study of 123 patients with documented PNES.
Disclosures: The study was funded by a practice research training fellowship from the American Academy of Neurology and the American Brain Foundation. Dr. Tolchin reported no other disclosures.
First visit for tuberous sclerosis complex comes months before diagnosis
HOUSTON – Many patients who eventually receive a diagnosis of tuberous sclerosis complex present with related complaints for months, or even years, before their condition is recognized and correctly diagnosed, according to a retrospective study.
The study, presented at the annual meeting of the American Epilepsy Society, found that patients with tuberous sclerosis complex (TSC) first sought care for TSC-related conditions an average of 7 months before they were diagnosed with the condition. Younger patients received the correct diagnosis sooner than did older patients: Treatment for TSC-related conditions preceded the diagnosis for 3.4 months for those aged 4 years or younger, compared with 5.5 months for those aged 25-29 years, and 21 months for those aged 80 years or older.
Seizures and skin conditions were common initial diagnoses among TSC patients, with 27% of patients aged 0-4 years being diagnosed with seizures prior to receiving their TSC diagnosis. The likelihood of prediagnosis visits for seizures decreased to less than 6% for older age groups. Seizures remained common post-TSC diagnosis among younger patients, with 38% of patients aged 0-4 years having any seizure diagnosis, while the rate fell through the lifespan to zero for those aged 80 or older.
James Wheless, MD, and his associates examined claims and enrollment data records from 2,163 patients diagnosed with TSC between January 2000 and December 2011. In addition to the frequently-diagnosed seizures seen in many TSC patients, skin conditions were diagnosed in 16.3% of patients before their eventual TSC diagnosis.
Other early conditions associated with TSC, according to the study’s multivariable analysis, included bone cysts, anxiety, and ADHD. However, wrote Dr. Wheless, chief of the department of pediatric neurology at the University of Tennessee Health Science Center, Memphis, and his coauthors, “at any point in time, patients with seizures were 2.9 times more likely to receive a TSC diagnosis than patients without seizures.”
The study was drawn from U.S. health plan databases that included both commercial and Medicare Advantage enrollees, and included patients through the lifespan. The date of the first recorded TSC diagnosis was the index date, and patients had to have at least 12 months of prediagnosis health plan enrollment to be included, or 6 months for those aged 2 years or younger. Data were collected for all pre-index visits (some of which stretched back to 1993), and for visits in the 12 months after the index visit.
The proportion of female patients ranged from fewer than half for those under 15 years (0-4 years, 46%; 5-9 years, 43%; 10-14 years, 48%) to 64% for those aged 80 years or older (P less than .001).
Dr. Wheless and his coauthors noted that the claims data used for the analysis “may not adequately capture clinical characteristics such as disease severity,” and that some patient data may have been lost if patients were disenrolled for periods of time during the study period.
The findings of the poster may prompt clinicians to consider TSC as a diagnosis; though rare, occurring in 1-2 per 6,000 live births, it’s thought to be an underrecognized disease entity. “Understanding the initial diagnoses experienced by TSC patients may help lead to earlier diagnosis and treatment of TSC,” Dr. Wheless and his coauthors wrote.
Novartis funded the study. Four study authors are employed by Optum, and one is employed by Novartis.
[email protected]
On Twitter @karioakes
HOUSTON – Many patients who eventually receive a diagnosis of tuberous sclerosis complex present with related complaints for months, or even years, before their condition is recognized and correctly diagnosed, according to a retrospective study.
The study, presented at the annual meeting of the American Epilepsy Society, found that patients with tuberous sclerosis complex (TSC) first sought care for TSC-related conditions an average of 7 months before they were diagnosed with the condition. Younger patients received the correct diagnosis sooner than did older patients: Treatment for TSC-related conditions preceded the diagnosis for 3.4 months for those aged 4 years or younger, compared with 5.5 months for those aged 25-29 years, and 21 months for those aged 80 years or older.
Seizures and skin conditions were common initial diagnoses among TSC patients, with 27% of patients aged 0-4 years being diagnosed with seizures prior to receiving their TSC diagnosis. The likelihood of prediagnosis visits for seizures decreased to less than 6% for older age groups. Seizures remained common post-TSC diagnosis among younger patients, with 38% of patients aged 0-4 years having any seizure diagnosis, while the rate fell through the lifespan to zero for those aged 80 or older.
James Wheless, MD, and his associates examined claims and enrollment data records from 2,163 patients diagnosed with TSC between January 2000 and December 2011. In addition to the frequently-diagnosed seizures seen in many TSC patients, skin conditions were diagnosed in 16.3% of patients before their eventual TSC diagnosis.
Other early conditions associated with TSC, according to the study’s multivariable analysis, included bone cysts, anxiety, and ADHD. However, wrote Dr. Wheless, chief of the department of pediatric neurology at the University of Tennessee Health Science Center, Memphis, and his coauthors, “at any point in time, patients with seizures were 2.9 times more likely to receive a TSC diagnosis than patients without seizures.”
The study was drawn from U.S. health plan databases that included both commercial and Medicare Advantage enrollees, and included patients through the lifespan. The date of the first recorded TSC diagnosis was the index date, and patients had to have at least 12 months of prediagnosis health plan enrollment to be included, or 6 months for those aged 2 years or younger. Data were collected for all pre-index visits (some of which stretched back to 1993), and for visits in the 12 months after the index visit.
The proportion of female patients ranged from fewer than half for those under 15 years (0-4 years, 46%; 5-9 years, 43%; 10-14 years, 48%) to 64% for those aged 80 years or older (P less than .001).
Dr. Wheless and his coauthors noted that the claims data used for the analysis “may not adequately capture clinical characteristics such as disease severity,” and that some patient data may have been lost if patients were disenrolled for periods of time during the study period.
The findings of the poster may prompt clinicians to consider TSC as a diagnosis; though rare, occurring in 1-2 per 6,000 live births, it’s thought to be an underrecognized disease entity. “Understanding the initial diagnoses experienced by TSC patients may help lead to earlier diagnosis and treatment of TSC,” Dr. Wheless and his coauthors wrote.
Novartis funded the study. Four study authors are employed by Optum, and one is employed by Novartis.
[email protected]
On Twitter @karioakes
HOUSTON – Many patients who eventually receive a diagnosis of tuberous sclerosis complex present with related complaints for months, or even years, before their condition is recognized and correctly diagnosed, according to a retrospective study.
The study, presented at the annual meeting of the American Epilepsy Society, found that patients with tuberous sclerosis complex (TSC) first sought care for TSC-related conditions an average of 7 months before they were diagnosed with the condition. Younger patients received the correct diagnosis sooner than did older patients: Treatment for TSC-related conditions preceded the diagnosis for 3.4 months for those aged 4 years or younger, compared with 5.5 months for those aged 25-29 years, and 21 months for those aged 80 years or older.
Seizures and skin conditions were common initial diagnoses among TSC patients, with 27% of patients aged 0-4 years being diagnosed with seizures prior to receiving their TSC diagnosis. The likelihood of prediagnosis visits for seizures decreased to less than 6% for older age groups. Seizures remained common post-TSC diagnosis among younger patients, with 38% of patients aged 0-4 years having any seizure diagnosis, while the rate fell through the lifespan to zero for those aged 80 or older.
James Wheless, MD, and his associates examined claims and enrollment data records from 2,163 patients diagnosed with TSC between January 2000 and December 2011. In addition to the frequently-diagnosed seizures seen in many TSC patients, skin conditions were diagnosed in 16.3% of patients before their eventual TSC diagnosis.
Other early conditions associated with TSC, according to the study’s multivariable analysis, included bone cysts, anxiety, and ADHD. However, wrote Dr. Wheless, chief of the department of pediatric neurology at the University of Tennessee Health Science Center, Memphis, and his coauthors, “at any point in time, patients with seizures were 2.9 times more likely to receive a TSC diagnosis than patients without seizures.”
The study was drawn from U.S. health plan databases that included both commercial and Medicare Advantage enrollees, and included patients through the lifespan. The date of the first recorded TSC diagnosis was the index date, and patients had to have at least 12 months of prediagnosis health plan enrollment to be included, or 6 months for those aged 2 years or younger. Data were collected for all pre-index visits (some of which stretched back to 1993), and for visits in the 12 months after the index visit.
The proportion of female patients ranged from fewer than half for those under 15 years (0-4 years, 46%; 5-9 years, 43%; 10-14 years, 48%) to 64% for those aged 80 years or older (P less than .001).
Dr. Wheless and his coauthors noted that the claims data used for the analysis “may not adequately capture clinical characteristics such as disease severity,” and that some patient data may have been lost if patients were disenrolled for periods of time during the study period.
The findings of the poster may prompt clinicians to consider TSC as a diagnosis; though rare, occurring in 1-2 per 6,000 live births, it’s thought to be an underrecognized disease entity. “Understanding the initial diagnoses experienced by TSC patients may help lead to earlier diagnosis and treatment of TSC,” Dr. Wheless and his coauthors wrote.
Novartis funded the study. Four study authors are employed by Optum, and one is employed by Novartis.
[email protected]
On Twitter @karioakes
FROM AES 2016
Key clinical point:
Major finding: Patients were seen an average of 6.9 months before they received their TSC diagnosis.
Data source: Retrospective review of claims and enrollment data from 2,163 patients with tuberous sclerosis.
Disclosures: Novartis funded the study. Four study authors are employed by Optum; one is employed by Novartis.
Machine learning beats clinical prediction of temporal lobe epilepsy surgery outcomes
HOUSTON – A machine learning interpretation of presurgical MRI studies did a better job of predicting which patients would have a successful outcome after anterior temporal lobectomy for temporal lobe epilepsy than did commonly-used clinical indicators in a prospective cohort study.
Xiaosong He, PhD, and his associates used two different machine learning classification methods to find two markers for thalamocortical connectedness that best predicted a good surgical outcome for temporal lobe epilepsy (TLE) in a small sample of patients. They presented their findings during a poster session of the annual meeting of the American Epilepsy Society.
After selecting a variety of possible predictors and building a model using resting state functional MRI (rsfMRI) data from 48 patients, the investigators then validated the prediction accuracies with rsfMRI data from 8 patients.
In predicting which TLE patients would have a good surgical outcome, models built with machine learning techniques using rsfMRI functional connectivity values had sensitivity ranging from 80% to 89% and specificity ranging from 52% to 57%. By comparison, models using clinical predictors only had sensitivity of 66% to 83% and specificity of 29% to 33%.
Dr. He and his coauthors dichotomized the surgical outcome for 56 patients who underwent TLE surgery into good outcome (n = 35) for those achieving and Engel class I and poor outcome (n = 21, class II-IV) at 1 year post surgery. All patients had a 5-minute rsfMRI scan before surgery.
MRI has been helpful in elucidating the importance of thalamocortical network pathology in TLE. Dr. He and his associates had previously used rsfMRI to examine the strength of functional connectivity between thalamic regions and their corresponding cortical regions in patients with TLE. Analysis of rsfMRI data of “both the left and right TLE groups showed that compared to controls there was a pattern of decreased thalamocortical [functional connectivity] in multiple thalamic segments,” wrote Dr. He and his collaborators (Epilepsia. 2015;56[10]:1571-9).
For the validation cohort, the two measures of connectedness found most predictive of a good surgical outcome were degree centrality and eigenvector centrality. In the graph theory and network analysis used in mapping functional connectivity, centrality refers to how highly connected one node, or data point, is to other data.
In the present study, the investigators used the Automated Anatomical Labeling cortical parcellation map to identify 45 cortical regions of interest per hemisphere, for a total of 90 cortical regions. They built a matrix with five topological parameters (global efficiency, global clustering coefficient, degree centrality, betweenness centrality, and eigenvector centrality) and the 90 cortical regions, yielding 272 variables. When nine commonly-used clinical predictors of surgical outcome (age, gender, handedness, laterality of TLE, epilepsy onset age and duration, seizure focality, interictal-spike type, and the presence of hippocampal sclerosis) were included, the model was made up of 281 variables.
The investigators used two different machine learning classification methods, called support vector machine and random forest, to build models that included various combinations of the 281 variables based on data from the initial 48 patients. The models were then tested with data from the remaining 8 patients.
Of the 35 patients with a good outcome, 18 had a left-sided epileptogenic temporal lobe; for the 21 patients with a poor outcome, the left temporal lobe was epileptogenic in 8. The mean age was similar for both groups: 41.25 years in those with good outcome, and 38.58 years in those with a poor outcome. Age at epilepsy onset also was similar, with each group having had epilepsy for about 17 years at the time of surgery. A total of 15 of the 20 patients with good outcome had seizure focality, compared with 10 of the 11 with poor outcome. Of those with a good outcome, 29 had an ipsilateral interactive spike, while 15 of those with poor outcomes had an ipsilateral interactive spike.
Since the random forest model best predicted surgical outcomes in the small sample size tested, the investigators plan to further fine-tune the random forest parameters to increase the robustness of their model.
Dr. He reported no conflicts of interest.
[email protected]
On Twitter @karioakes
HOUSTON – A machine learning interpretation of presurgical MRI studies did a better job of predicting which patients would have a successful outcome after anterior temporal lobectomy for temporal lobe epilepsy than did commonly-used clinical indicators in a prospective cohort study.
Xiaosong He, PhD, and his associates used two different machine learning classification methods to find two markers for thalamocortical connectedness that best predicted a good surgical outcome for temporal lobe epilepsy (TLE) in a small sample of patients. They presented their findings during a poster session of the annual meeting of the American Epilepsy Society.
After selecting a variety of possible predictors and building a model using resting state functional MRI (rsfMRI) data from 48 patients, the investigators then validated the prediction accuracies with rsfMRI data from 8 patients.
In predicting which TLE patients would have a good surgical outcome, models built with machine learning techniques using rsfMRI functional connectivity values had sensitivity ranging from 80% to 89% and specificity ranging from 52% to 57%. By comparison, models using clinical predictors only had sensitivity of 66% to 83% and specificity of 29% to 33%.
Dr. He and his coauthors dichotomized the surgical outcome for 56 patients who underwent TLE surgery into good outcome (n = 35) for those achieving and Engel class I and poor outcome (n = 21, class II-IV) at 1 year post surgery. All patients had a 5-minute rsfMRI scan before surgery.
MRI has been helpful in elucidating the importance of thalamocortical network pathology in TLE. Dr. He and his associates had previously used rsfMRI to examine the strength of functional connectivity between thalamic regions and their corresponding cortical regions in patients with TLE. Analysis of rsfMRI data of “both the left and right TLE groups showed that compared to controls there was a pattern of decreased thalamocortical [functional connectivity] in multiple thalamic segments,” wrote Dr. He and his collaborators (Epilepsia. 2015;56[10]:1571-9).
For the validation cohort, the two measures of connectedness found most predictive of a good surgical outcome were degree centrality and eigenvector centrality. In the graph theory and network analysis used in mapping functional connectivity, centrality refers to how highly connected one node, or data point, is to other data.
In the present study, the investigators used the Automated Anatomical Labeling cortical parcellation map to identify 45 cortical regions of interest per hemisphere, for a total of 90 cortical regions. They built a matrix with five topological parameters (global efficiency, global clustering coefficient, degree centrality, betweenness centrality, and eigenvector centrality) and the 90 cortical regions, yielding 272 variables. When nine commonly-used clinical predictors of surgical outcome (age, gender, handedness, laterality of TLE, epilepsy onset age and duration, seizure focality, interictal-spike type, and the presence of hippocampal sclerosis) were included, the model was made up of 281 variables.
The investigators used two different machine learning classification methods, called support vector machine and random forest, to build models that included various combinations of the 281 variables based on data from the initial 48 patients. The models were then tested with data from the remaining 8 patients.
Of the 35 patients with a good outcome, 18 had a left-sided epileptogenic temporal lobe; for the 21 patients with a poor outcome, the left temporal lobe was epileptogenic in 8. The mean age was similar for both groups: 41.25 years in those with good outcome, and 38.58 years in those with a poor outcome. Age at epilepsy onset also was similar, with each group having had epilepsy for about 17 years at the time of surgery. A total of 15 of the 20 patients with good outcome had seizure focality, compared with 10 of the 11 with poor outcome. Of those with a good outcome, 29 had an ipsilateral interactive spike, while 15 of those with poor outcomes had an ipsilateral interactive spike.
Since the random forest model best predicted surgical outcomes in the small sample size tested, the investigators plan to further fine-tune the random forest parameters to increase the robustness of their model.
Dr. He reported no conflicts of interest.
[email protected]
On Twitter @karioakes
HOUSTON – A machine learning interpretation of presurgical MRI studies did a better job of predicting which patients would have a successful outcome after anterior temporal lobectomy for temporal lobe epilepsy than did commonly-used clinical indicators in a prospective cohort study.
Xiaosong He, PhD, and his associates used two different machine learning classification methods to find two markers for thalamocortical connectedness that best predicted a good surgical outcome for temporal lobe epilepsy (TLE) in a small sample of patients. They presented their findings during a poster session of the annual meeting of the American Epilepsy Society.
After selecting a variety of possible predictors and building a model using resting state functional MRI (rsfMRI) data from 48 patients, the investigators then validated the prediction accuracies with rsfMRI data from 8 patients.
In predicting which TLE patients would have a good surgical outcome, models built with machine learning techniques using rsfMRI functional connectivity values had sensitivity ranging from 80% to 89% and specificity ranging from 52% to 57%. By comparison, models using clinical predictors only had sensitivity of 66% to 83% and specificity of 29% to 33%.
Dr. He and his coauthors dichotomized the surgical outcome for 56 patients who underwent TLE surgery into good outcome (n = 35) for those achieving and Engel class I and poor outcome (n = 21, class II-IV) at 1 year post surgery. All patients had a 5-minute rsfMRI scan before surgery.
MRI has been helpful in elucidating the importance of thalamocortical network pathology in TLE. Dr. He and his associates had previously used rsfMRI to examine the strength of functional connectivity between thalamic regions and their corresponding cortical regions in patients with TLE. Analysis of rsfMRI data of “both the left and right TLE groups showed that compared to controls there was a pattern of decreased thalamocortical [functional connectivity] in multiple thalamic segments,” wrote Dr. He and his collaborators (Epilepsia. 2015;56[10]:1571-9).
For the validation cohort, the two measures of connectedness found most predictive of a good surgical outcome were degree centrality and eigenvector centrality. In the graph theory and network analysis used in mapping functional connectivity, centrality refers to how highly connected one node, or data point, is to other data.
In the present study, the investigators used the Automated Anatomical Labeling cortical parcellation map to identify 45 cortical regions of interest per hemisphere, for a total of 90 cortical regions. They built a matrix with five topological parameters (global efficiency, global clustering coefficient, degree centrality, betweenness centrality, and eigenvector centrality) and the 90 cortical regions, yielding 272 variables. When nine commonly-used clinical predictors of surgical outcome (age, gender, handedness, laterality of TLE, epilepsy onset age and duration, seizure focality, interictal-spike type, and the presence of hippocampal sclerosis) were included, the model was made up of 281 variables.
The investigators used two different machine learning classification methods, called support vector machine and random forest, to build models that included various combinations of the 281 variables based on data from the initial 48 patients. The models were then tested with data from the remaining 8 patients.
Of the 35 patients with a good outcome, 18 had a left-sided epileptogenic temporal lobe; for the 21 patients with a poor outcome, the left temporal lobe was epileptogenic in 8. The mean age was similar for both groups: 41.25 years in those with good outcome, and 38.58 years in those with a poor outcome. Age at epilepsy onset also was similar, with each group having had epilepsy for about 17 years at the time of surgery. A total of 15 of the 20 patients with good outcome had seizure focality, compared with 10 of the 11 with poor outcome. Of those with a good outcome, 29 had an ipsilateral interactive spike, while 15 of those with poor outcomes had an ipsilateral interactive spike.
Since the random forest model best predicted surgical outcomes in the small sample size tested, the investigators plan to further fine-tune the random forest parameters to increase the robustness of their model.
Dr. He reported no conflicts of interest.
[email protected]
On Twitter @karioakes
AT AES 2016
Key clinical point:
Major finding: Models built with machine learning techniques using resting state fMRI functional connectivity values had sensitivity ranging from 80% to 89% and specificity ranging from 52% to 57%.
Data source: A prospective study of 56 patients with temporal lobe epilepsy.
Disclosures: Dr. He reported no conflicts of interest.
Add-on fenfluramine reduces seizure frequency in Dravet syndrome
HOUSTON – Low-dose fenfluramine was found to reduce seizures significantly among a small cohort with Dravet syndrome without the appearance of valvular abnormalities or pulmonary hypertension, according to a prospective study presented at a poster session of the annual meeting of the American Epilepsy Society.
Six of nine Dravet syndrome (DS) patients (66%) had at least a 50% reduction in major motor seizure frequency for at least 90% of the period during which they took fenfluramine. Five of the nine DS patients (56%) experienced a reduction in major motor seizure frequency of 75% or more for at least 60% of the median 1.9 years they were on fenfluramine.
According to lead author An-Sofie Schoonjans, MD, and her collaborators, the results suggest that “low-dose fenfluramine provides significant improvement in seizure frequency while being generally well tolerated in DS patients.”
The study criteria included patients aged 6 months to 50 years who had a DS diagnosis; enrollees ranged in age from 1.2 to 29.8 years when starting fenfluramine. Though criteria allowed enrollment of patients with and without a mutation in the SCN1A gene, all participants did have a de novo mutation of the SCN1A gene, according to Dr. Schoonjans of the department of pediatric neurology at Antwerp (Belgium) University Hospital and her colleagues. They wrote that mutations in the gene, which encodes the alpha subunit of type 1 voltage-gated sodium channels, are found in about 80% of DS patients.
During the 3-month run-in period that began the study, patients had a median seizure frequency of 15 seizures per month. Patients remained on their baseline antiepilepsy regimen during the run-in period and throughout the study, with fenfluramine used as add-on therapy. At baseline, all patients were taking valproic acid and at least one other antiepileptic medication; three patients were taking four medications and one was taking five medications. Three patients also had vagal nerve stimulators with stable settings.
Throughout the study period, patients or their caregivers kept a seizure diary, recording major motor seizures. Those keeping the diary were instructed to record all tonic-clonic, tonic, atonic, and myoclonic seizures lasting more than 30 seconds.
Three months after beginning treatment, the study population’s median seizure frequency fell to 2.0 per month (–84%). Frequency fell further during the first year, to 1.0 per month (–79%; a smaller percent reduction because data were not available for this time period for the patient with the highest seizure frequency). For the total treatment period, the median seizure frequency was 1.9 per month (–76%). The reduction in seizure frequency was statistically significant at all time points (P less than .05; compared with baseline).
Fenfluramine was generally well-tolerated. Five patients experienced somnolence, and four had loss of appetite.
To track cardiovascular safety, all patients had echocardiographs at baseline and every 3 months during the first year of treatment. Echocardiographs were performed every 6 months during the second year, and annually thereafter. One patient had systolic dysfunction characterized by a reduced ejection fraction (53%) and fractional shortening (26%), findings of “no clinical significance,” according to Dr. Schoonjans and her colleagues.
Fenfluramine was part of an oral weight loss drug combination, along with phentermine. The combo, known as “fen-phen,” was associated with increased rates of pulmonary hypertension and valve disease, particularly aortic valve thickening and regurgitation. It was withdrawn from the market in 1997. Though pulmonary hypertension would frequently resolve after discontinuing fen-phen, not all patients with valvulopathy experienced resolution, and case reports of patients with the aortic valve thickening typically seen with fenfluramine are still surfacing many years after the drug’s discontinuation (e.g., Tex Heart Inst J. 2011;38[5]:581-3).
Fenfluramine was typically given at doses up to 60 mg when used with phentermine for weight loss. The dosing for Dravet syndrome patients in this study was much lower and weight based, ranging from 0.1 to 1.0 mg/kg per day, with a maximum permitted dose of 20 mg/day.
Fenfluramine is a serotonin releaser, and serotonin is known to modulate the action of voltage-gated sodium channels. However, the exact mechanism by which the drug reduces seizure frequency is not known. Clinical trials are underway in the United States for both DS and Lennox Gastaut epilepsy, and fenfluramine has been granted orphan drug status in the United States and Europe, according to an announcement from Zogenix, the drug’s manufacturer.
The study was funded by Zogenix, which holds a Royal Decree to dispense the drug under the study conditions in Belgium, where the study took place. Zogenix also funded writing and editorial assistance for the poster presentation.
[email protected]
On Twitter @karioakes
HOUSTON – Low-dose fenfluramine was found to reduce seizures significantly among a small cohort with Dravet syndrome without the appearance of valvular abnormalities or pulmonary hypertension, according to a prospective study presented at a poster session of the annual meeting of the American Epilepsy Society.
Six of nine Dravet syndrome (DS) patients (66%) had at least a 50% reduction in major motor seizure frequency for at least 90% of the period during which they took fenfluramine. Five of the nine DS patients (56%) experienced a reduction in major motor seizure frequency of 75% or more for at least 60% of the median 1.9 years they were on fenfluramine.
According to lead author An-Sofie Schoonjans, MD, and her collaborators, the results suggest that “low-dose fenfluramine provides significant improvement in seizure frequency while being generally well tolerated in DS patients.”
The study criteria included patients aged 6 months to 50 years who had a DS diagnosis; enrollees ranged in age from 1.2 to 29.8 years when starting fenfluramine. Though criteria allowed enrollment of patients with and without a mutation in the SCN1A gene, all participants did have a de novo mutation of the SCN1A gene, according to Dr. Schoonjans of the department of pediatric neurology at Antwerp (Belgium) University Hospital and her colleagues. They wrote that mutations in the gene, which encodes the alpha subunit of type 1 voltage-gated sodium channels, are found in about 80% of DS patients.
During the 3-month run-in period that began the study, patients had a median seizure frequency of 15 seizures per month. Patients remained on their baseline antiepilepsy regimen during the run-in period and throughout the study, with fenfluramine used as add-on therapy. At baseline, all patients were taking valproic acid and at least one other antiepileptic medication; three patients were taking four medications and one was taking five medications. Three patients also had vagal nerve stimulators with stable settings.
Throughout the study period, patients or their caregivers kept a seizure diary, recording major motor seizures. Those keeping the diary were instructed to record all tonic-clonic, tonic, atonic, and myoclonic seizures lasting more than 30 seconds.
Three months after beginning treatment, the study population’s median seizure frequency fell to 2.0 per month (–84%). Frequency fell further during the first year, to 1.0 per month (–79%; a smaller percent reduction because data were not available for this time period for the patient with the highest seizure frequency). For the total treatment period, the median seizure frequency was 1.9 per month (–76%). The reduction in seizure frequency was statistically significant at all time points (P less than .05; compared with baseline).
Fenfluramine was generally well-tolerated. Five patients experienced somnolence, and four had loss of appetite.
To track cardiovascular safety, all patients had echocardiographs at baseline and every 3 months during the first year of treatment. Echocardiographs were performed every 6 months during the second year, and annually thereafter. One patient had systolic dysfunction characterized by a reduced ejection fraction (53%) and fractional shortening (26%), findings of “no clinical significance,” according to Dr. Schoonjans and her colleagues.
Fenfluramine was part of an oral weight loss drug combination, along with phentermine. The combo, known as “fen-phen,” was associated with increased rates of pulmonary hypertension and valve disease, particularly aortic valve thickening and regurgitation. It was withdrawn from the market in 1997. Though pulmonary hypertension would frequently resolve after discontinuing fen-phen, not all patients with valvulopathy experienced resolution, and case reports of patients with the aortic valve thickening typically seen with fenfluramine are still surfacing many years after the drug’s discontinuation (e.g., Tex Heart Inst J. 2011;38[5]:581-3).
Fenfluramine was typically given at doses up to 60 mg when used with phentermine for weight loss. The dosing for Dravet syndrome patients in this study was much lower and weight based, ranging from 0.1 to 1.0 mg/kg per day, with a maximum permitted dose of 20 mg/day.
Fenfluramine is a serotonin releaser, and serotonin is known to modulate the action of voltage-gated sodium channels. However, the exact mechanism by which the drug reduces seizure frequency is not known. Clinical trials are underway in the United States for both DS and Lennox Gastaut epilepsy, and fenfluramine has been granted orphan drug status in the United States and Europe, according to an announcement from Zogenix, the drug’s manufacturer.
The study was funded by Zogenix, which holds a Royal Decree to dispense the drug under the study conditions in Belgium, where the study took place. Zogenix also funded writing and editorial assistance for the poster presentation.
[email protected]
On Twitter @karioakes
HOUSTON – Low-dose fenfluramine was found to reduce seizures significantly among a small cohort with Dravet syndrome without the appearance of valvular abnormalities or pulmonary hypertension, according to a prospective study presented at a poster session of the annual meeting of the American Epilepsy Society.
Six of nine Dravet syndrome (DS) patients (66%) had at least a 50% reduction in major motor seizure frequency for at least 90% of the period during which they took fenfluramine. Five of the nine DS patients (56%) experienced a reduction in major motor seizure frequency of 75% or more for at least 60% of the median 1.9 years they were on fenfluramine.
According to lead author An-Sofie Schoonjans, MD, and her collaborators, the results suggest that “low-dose fenfluramine provides significant improvement in seizure frequency while being generally well tolerated in DS patients.”
The study criteria included patients aged 6 months to 50 years who had a DS diagnosis; enrollees ranged in age from 1.2 to 29.8 years when starting fenfluramine. Though criteria allowed enrollment of patients with and without a mutation in the SCN1A gene, all participants did have a de novo mutation of the SCN1A gene, according to Dr. Schoonjans of the department of pediatric neurology at Antwerp (Belgium) University Hospital and her colleagues. They wrote that mutations in the gene, which encodes the alpha subunit of type 1 voltage-gated sodium channels, are found in about 80% of DS patients.
During the 3-month run-in period that began the study, patients had a median seizure frequency of 15 seizures per month. Patients remained on their baseline antiepilepsy regimen during the run-in period and throughout the study, with fenfluramine used as add-on therapy. At baseline, all patients were taking valproic acid and at least one other antiepileptic medication; three patients were taking four medications and one was taking five medications. Three patients also had vagal nerve stimulators with stable settings.
Throughout the study period, patients or their caregivers kept a seizure diary, recording major motor seizures. Those keeping the diary were instructed to record all tonic-clonic, tonic, atonic, and myoclonic seizures lasting more than 30 seconds.
Three months after beginning treatment, the study population’s median seizure frequency fell to 2.0 per month (–84%). Frequency fell further during the first year, to 1.0 per month (–79%; a smaller percent reduction because data were not available for this time period for the patient with the highest seizure frequency). For the total treatment period, the median seizure frequency was 1.9 per month (–76%). The reduction in seizure frequency was statistically significant at all time points (P less than .05; compared with baseline).
Fenfluramine was generally well-tolerated. Five patients experienced somnolence, and four had loss of appetite.
To track cardiovascular safety, all patients had echocardiographs at baseline and every 3 months during the first year of treatment. Echocardiographs were performed every 6 months during the second year, and annually thereafter. One patient had systolic dysfunction characterized by a reduced ejection fraction (53%) and fractional shortening (26%), findings of “no clinical significance,” according to Dr. Schoonjans and her colleagues.
Fenfluramine was part of an oral weight loss drug combination, along with phentermine. The combo, known as “fen-phen,” was associated with increased rates of pulmonary hypertension and valve disease, particularly aortic valve thickening and regurgitation. It was withdrawn from the market in 1997. Though pulmonary hypertension would frequently resolve after discontinuing fen-phen, not all patients with valvulopathy experienced resolution, and case reports of patients with the aortic valve thickening typically seen with fenfluramine are still surfacing many years after the drug’s discontinuation (e.g., Tex Heart Inst J. 2011;38[5]:581-3).
Fenfluramine was typically given at doses up to 60 mg when used with phentermine for weight loss. The dosing for Dravet syndrome patients in this study was much lower and weight based, ranging from 0.1 to 1.0 mg/kg per day, with a maximum permitted dose of 20 mg/day.
Fenfluramine is a serotonin releaser, and serotonin is known to modulate the action of voltage-gated sodium channels. However, the exact mechanism by which the drug reduces seizure frequency is not known. Clinical trials are underway in the United States for both DS and Lennox Gastaut epilepsy, and fenfluramine has been granted orphan drug status in the United States and Europe, according to an announcement from Zogenix, the drug’s manufacturer.
The study was funded by Zogenix, which holds a Royal Decree to dispense the drug under the study conditions in Belgium, where the study took place. Zogenix also funded writing and editorial assistance for the poster presentation.
[email protected]
On Twitter @karioakes
AT AES 2016
Key clinical point:
Major finding: Six of nine patients (66%) had a reduction in seizure frequency of at least 50% for at least 90% of the time they were taking fenfluramine.
Data source: Prospective cohort study of nine patients with Dravet syndrome who took fenfluramine as add-on therapy for a median 1.9 years.
Disclosures: The study was funded by Zogenix, which funded editorial and writing support for the poster presentation.
FDA bans powdered gloves
The Food and Drug Administration has banned powdered gloves for use in health care settings, citing “numerous risks to patients and health care workers.” The ban extends to gloves currently in commercial distribution and in the hands of the ultimate user, meaning powdered gloves will have to be pulled from examination rooms and operating theaters.
“A thorough review of all currently available information supports FDA’s conclusion that powdered surgeon’s gloves, powdered patient examination gloves, and absorbable powder for lubricating a surgeon’s glove should be banned,” according to a FDA final rule available now online and scheduled for publication in the Federal Register on Dec. 19, 2016. The ban will become effective 30 days after the document’s publication in the Federal Register.
Notes the final document, “The benefits of powdered gloves appear to only include greater ease of donning and doffing, decreased tackiness, and a degree of added comfort, which FDA believes are nominal when compared to the risks posed by these devices.”
Since viable nonpowdered alternatives exist, the FDA believes that the ban would not have significant economic impact and that shortages should not affect care delivery.
Many nonpowdered gloves, said the FDA, now “have the same level of protection, dexterity, and performance” as powdered gloves.
Powder may still be used in the glove manufacturing process, but the FDA continues to recommend that no more than 2 mg of residual powder per glove remains after the manufacturing process.
Though the final document banning powdered gloves notes that the FDA received many comments asking for a ban of all natural rubber latex (NRL) gloves, the ban applied only to powdered gloves. The FDA noted that NRL gloves already must carry a statement alerting users to the risks of allergic reaction, and also noted that eliminating powder from NRL gloves reduces the risk of latex sensitization.
In explaining its analysis of the costs and benefits of the powdered glove ban, the FDA estimated that the annual net benefits would range between $26.8 million and $31.8 million.
When this ban comes into force, it will be only the second such ban; the first was the 1983 ban of prosthetic hair fibers, which were found to provide no public health benefit.
[email protected]
On Twitter @karioakes
The Food and Drug Administration has banned powdered gloves for use in health care settings, citing “numerous risks to patients and health care workers.” The ban extends to gloves currently in commercial distribution and in the hands of the ultimate user, meaning powdered gloves will have to be pulled from examination rooms and operating theaters.
“A thorough review of all currently available information supports FDA’s conclusion that powdered surgeon’s gloves, powdered patient examination gloves, and absorbable powder for lubricating a surgeon’s glove should be banned,” according to a FDA final rule available now online and scheduled for publication in the Federal Register on Dec. 19, 2016. The ban will become effective 30 days after the document’s publication in the Federal Register.
Notes the final document, “The benefits of powdered gloves appear to only include greater ease of donning and doffing, decreased tackiness, and a degree of added comfort, which FDA believes are nominal when compared to the risks posed by these devices.”
Since viable nonpowdered alternatives exist, the FDA believes that the ban would not have significant economic impact and that shortages should not affect care delivery.
Many nonpowdered gloves, said the FDA, now “have the same level of protection, dexterity, and performance” as powdered gloves.
Powder may still be used in the glove manufacturing process, but the FDA continues to recommend that no more than 2 mg of residual powder per glove remains after the manufacturing process.
Though the final document banning powdered gloves notes that the FDA received many comments asking for a ban of all natural rubber latex (NRL) gloves, the ban applied only to powdered gloves. The FDA noted that NRL gloves already must carry a statement alerting users to the risks of allergic reaction, and also noted that eliminating powder from NRL gloves reduces the risk of latex sensitization.
In explaining its analysis of the costs and benefits of the powdered glove ban, the FDA estimated that the annual net benefits would range between $26.8 million and $31.8 million.
When this ban comes into force, it will be only the second such ban; the first was the 1983 ban of prosthetic hair fibers, which were found to provide no public health benefit.
[email protected]
On Twitter @karioakes
The Food and Drug Administration has banned powdered gloves for use in health care settings, citing “numerous risks to patients and health care workers.” The ban extends to gloves currently in commercial distribution and in the hands of the ultimate user, meaning powdered gloves will have to be pulled from examination rooms and operating theaters.
“A thorough review of all currently available information supports FDA’s conclusion that powdered surgeon’s gloves, powdered patient examination gloves, and absorbable powder for lubricating a surgeon’s glove should be banned,” according to a FDA final rule available now online and scheduled for publication in the Federal Register on Dec. 19, 2016. The ban will become effective 30 days after the document’s publication in the Federal Register.
Notes the final document, “The benefits of powdered gloves appear to only include greater ease of donning and doffing, decreased tackiness, and a degree of added comfort, which FDA believes are nominal when compared to the risks posed by these devices.”
Since viable nonpowdered alternatives exist, the FDA believes that the ban would not have significant economic impact and that shortages should not affect care delivery.
Many nonpowdered gloves, said the FDA, now “have the same level of protection, dexterity, and performance” as powdered gloves.
Powder may still be used in the glove manufacturing process, but the FDA continues to recommend that no more than 2 mg of residual powder per glove remains after the manufacturing process.
Though the final document banning powdered gloves notes that the FDA received many comments asking for a ban of all natural rubber latex (NRL) gloves, the ban applied only to powdered gloves. The FDA noted that NRL gloves already must carry a statement alerting users to the risks of allergic reaction, and also noted that eliminating powder from NRL gloves reduces the risk of latex sensitization.
In explaining its analysis of the costs and benefits of the powdered glove ban, the FDA estimated that the annual net benefits would range between $26.8 million and $31.8 million.
When this ban comes into force, it will be only the second such ban; the first was the 1983 ban of prosthetic hair fibers, which were found to provide no public health benefit.
[email protected]
On Twitter @karioakes
More tricuspid valve regurgitation should be fixed
CHICAGO – Fixing the tricuspid valve should be part of left-sided heart operations in many cases of functional tricuspid regurgitation, but study data and international guidelines supporting the practice are too frequently ignored, said Steven Bolling, MD.
Speaking during Heart Valve Summit 2016, Dr. Bolling said that of the approximately four million U.S. individuals with mitral regurgitation, about 1.6 million, or 40%, have concomitant tricuspid regurgitation (TR). Yet, he said, only about 7,000 concomitant tricuspid valve (TV) repairs are performed in the 60,000 patients receiving mitral valve (MV) repair surgery annually, for a TV repair rate of less than 12%. “Tricuspid regurgitation is ignored,” said Dr. Bolling, a conference organizer and professor of surgery at the University of Michigan, Ann Arbor.
A 2015 study followed 645 consecutive patients who underwent primary repair of degenerative mitral regurgitation. The patients who had concomitant TVR, he said, “had far less TR, better right ventricle function, and it’s safe. There was lower mortality and morbidity” (J Am Coll Cardiol. 2015 May 12;65[18]:1931-8).
Citing a study of 5,589 patients undergoing surgery for mitral valve regurgitation only, 16% of these had severe – grade 3-4+ – TR preoperatively. However, at discharge, 62% of those had severe residual TR. Despite a “good” mitral result, said Dr. Bolling, multiple studies dating back to the 1980s have demonstrated that surgical repair of just the mitral valve still results in functional tricuspid regurgitation (FTR) rates of up to 67%. “There’s no guarantee of FTR ‘getting better,’” said Dr. Bolling.
The problem lies fundamentally in the annular dilation and change of shape of the tricuspid annulus, and so these issues must be addressed for a good functional result, he said. This dilation and distortion has been shown to occur in up to 75% of all cases of MR (Circulation. 2006;114:1-492).
“Placing an ‘undersized’ tricuspid ring is actually restoring normal sizing to the annulus,” said Dr. Bolling. The normal tricuspid annular dimension is 2.8 cm, plus or minus 0.5 cm, he said. Patients fare better both in the immediate postoperative period and at follow-up with an “undersized” TV repair for FTR, he said.
And surgeons shouldn’t worry about stenosis with an “undersized” TV repair, he said. High school geometry shows that a 26-mm valve diameter yields an area of about 4 square cm, for a 2- to 3-mm gradient, said Dr. Bolling.
Detection of tricuspid regurgitation can itself be a tricky prospect, because tricuspid regurgitation is dynamic. “You should look for functional tricuspid regurgitation preoperatively,” said Dr. Bolling. “Under anesthesia, four-plus TR can become mild.” Accordingly, any significant intraoperative TR or a dilated annulus should be considered indications for tricuspid valve repair, he said.
Though adding TV repair to mitral surgery may add some complexity, it does not necessarily add risk, said Dr. Bolling, citing a study of 110 matched patients with FTR that found a trend toward lower 30-day mortality for combined repair, when compared to mitral repair only (2% versus 8.5%, P = .2).
However, the single-intervention group had a 40% rate of tricuspid progression compared to 5% when both valves were repaired, and the 5-year survival rate was higher for those who had the combined surgery (74% versus 45%; Ann Thorac Surg. 2009 Mar;87[3]:698-703).
According to American College of Cardiology/American Heart Association (ACC/AHA) guidelines for managing valvular heart disease, which were last updated in 2014, patients with severe TR who are undergoing left-sided valve surgery should have concomitant TV repair, a class I recommendation.
The European Society of Cardiology and the European Association for Cardio-Thoracic Surgery (ESC/EACTS) 2012 guidelines are in accord with the ACC/AHA for this population, also issuing a class I recommendation.
For patients with greater than mild TR who have tricuspid annular dilation or right-sided heart failure, TV repair is a class IIa recommendation, according to the ACC/AHA guidelines. For patients with FTR who also have either pulmonary hypertension or right ventricular dilation or dysfunction, TV repair is an ACC/AHA class IIb recommendation.
In the European guidelines, patients with moderate secondary TR with a tricuspid annulus over 40 mm in diameter who are undergoing left-sided valve surgery, or who have right ventricular dilation or dysfunction, should undergo TV repair. This is a class IIa recommendation in the ESC/EACTS schema.
Dr. Bolling reported financial relationships with the Sorin Group, Medtronic, and Edwards Lifesciences.
[email protected]
On Twitter @karioakes
CHICAGO – Fixing the tricuspid valve should be part of left-sided heart operations in many cases of functional tricuspid regurgitation, but study data and international guidelines supporting the practice are too frequently ignored, said Steven Bolling, MD.
Speaking during Heart Valve Summit 2016, Dr. Bolling said that of the approximately four million U.S. individuals with mitral regurgitation, about 1.6 million, or 40%, have concomitant tricuspid regurgitation (TR). Yet, he said, only about 7,000 concomitant tricuspid valve (TV) repairs are performed in the 60,000 patients receiving mitral valve (MV) repair surgery annually, for a TV repair rate of less than 12%. “Tricuspid regurgitation is ignored,” said Dr. Bolling, a conference organizer and professor of surgery at the University of Michigan, Ann Arbor.
A 2015 study followed 645 consecutive patients who underwent primary repair of degenerative mitral regurgitation. The patients who had concomitant TVR, he said, “had far less TR, better right ventricle function, and it’s safe. There was lower mortality and morbidity” (J Am Coll Cardiol. 2015 May 12;65[18]:1931-8).
Citing a study of 5,589 patients undergoing surgery for mitral valve regurgitation only, 16% of these had severe – grade 3-4+ – TR preoperatively. However, at discharge, 62% of those had severe residual TR. Despite a “good” mitral result, said Dr. Bolling, multiple studies dating back to the 1980s have demonstrated that surgical repair of just the mitral valve still results in functional tricuspid regurgitation (FTR) rates of up to 67%. “There’s no guarantee of FTR ‘getting better,’” said Dr. Bolling.
The problem lies fundamentally in the annular dilation and change of shape of the tricuspid annulus, and so these issues must be addressed for a good functional result, he said. This dilation and distortion has been shown to occur in up to 75% of all cases of MR (Circulation. 2006;114:1-492).
“Placing an ‘undersized’ tricuspid ring is actually restoring normal sizing to the annulus,” said Dr. Bolling. The normal tricuspid annular dimension is 2.8 cm, plus or minus 0.5 cm, he said. Patients fare better both in the immediate postoperative period and at follow-up with an “undersized” TV repair for FTR, he said.
And surgeons shouldn’t worry about stenosis with an “undersized” TV repair, he said. High school geometry shows that a 26-mm valve diameter yields an area of about 4 square cm, for a 2- to 3-mm gradient, said Dr. Bolling.
Detection of tricuspid regurgitation can itself be a tricky prospect, because tricuspid regurgitation is dynamic. “You should look for functional tricuspid regurgitation preoperatively,” said Dr. Bolling. “Under anesthesia, four-plus TR can become mild.” Accordingly, any significant intraoperative TR or a dilated annulus should be considered indications for tricuspid valve repair, he said.
Though adding TV repair to mitral surgery may add some complexity, it does not necessarily add risk, said Dr. Bolling, citing a study of 110 matched patients with FTR that found a trend toward lower 30-day mortality for combined repair, when compared to mitral repair only (2% versus 8.5%, P = .2).
However, the single-intervention group had a 40% rate of tricuspid progression compared to 5% when both valves were repaired, and the 5-year survival rate was higher for those who had the combined surgery (74% versus 45%; Ann Thorac Surg. 2009 Mar;87[3]:698-703).
According to American College of Cardiology/American Heart Association (ACC/AHA) guidelines for managing valvular heart disease, which were last updated in 2014, patients with severe TR who are undergoing left-sided valve surgery should have concomitant TV repair, a class I recommendation.
The European Society of Cardiology and the European Association for Cardio-Thoracic Surgery (ESC/EACTS) 2012 guidelines are in accord with the ACC/AHA for this population, also issuing a class I recommendation.
For patients with greater than mild TR who have tricuspid annular dilation or right-sided heart failure, TV repair is a class IIa recommendation, according to the ACC/AHA guidelines. For patients with FTR who also have either pulmonary hypertension or right ventricular dilation or dysfunction, TV repair is an ACC/AHA class IIb recommendation.
In the European guidelines, patients with moderate secondary TR with a tricuspid annulus over 40 mm in diameter who are undergoing left-sided valve surgery, or who have right ventricular dilation or dysfunction, should undergo TV repair. This is a class IIa recommendation in the ESC/EACTS schema.
Dr. Bolling reported financial relationships with the Sorin Group, Medtronic, and Edwards Lifesciences.
[email protected]
On Twitter @karioakes
CHICAGO – Fixing the tricuspid valve should be part of left-sided heart operations in many cases of functional tricuspid regurgitation, but study data and international guidelines supporting the practice are too frequently ignored, said Steven Bolling, MD.
Speaking during Heart Valve Summit 2016, Dr. Bolling said that of the approximately four million U.S. individuals with mitral regurgitation, about 1.6 million, or 40%, have concomitant tricuspid regurgitation (TR). Yet, he said, only about 7,000 concomitant tricuspid valve (TV) repairs are performed in the 60,000 patients receiving mitral valve (MV) repair surgery annually, for a TV repair rate of less than 12%. “Tricuspid regurgitation is ignored,” said Dr. Bolling, a conference organizer and professor of surgery at the University of Michigan, Ann Arbor.
A 2015 study followed 645 consecutive patients who underwent primary repair of degenerative mitral regurgitation. The patients who had concomitant TVR, he said, “had far less TR, better right ventricle function, and it’s safe. There was lower mortality and morbidity” (J Am Coll Cardiol. 2015 May 12;65[18]:1931-8).
Citing a study of 5,589 patients undergoing surgery for mitral valve regurgitation only, 16% of these had severe – grade 3-4+ – TR preoperatively. However, at discharge, 62% of those had severe residual TR. Despite a “good” mitral result, said Dr. Bolling, multiple studies dating back to the 1980s have demonstrated that surgical repair of just the mitral valve still results in functional tricuspid regurgitation (FTR) rates of up to 67%. “There’s no guarantee of FTR ‘getting better,’” said Dr. Bolling.
The problem lies fundamentally in the annular dilation and change of shape of the tricuspid annulus, and so these issues must be addressed for a good functional result, he said. This dilation and distortion has been shown to occur in up to 75% of all cases of MR (Circulation. 2006;114:1-492).
“Placing an ‘undersized’ tricuspid ring is actually restoring normal sizing to the annulus,” said Dr. Bolling. The normal tricuspid annular dimension is 2.8 cm, plus or minus 0.5 cm, he said. Patients fare better both in the immediate postoperative period and at follow-up with an “undersized” TV repair for FTR, he said.
And surgeons shouldn’t worry about stenosis with an “undersized” TV repair, he said. High school geometry shows that a 26-mm valve diameter yields an area of about 4 square cm, for a 2- to 3-mm gradient, said Dr. Bolling.
Detection of tricuspid regurgitation can itself be a tricky prospect, because tricuspid regurgitation is dynamic. “You should look for functional tricuspid regurgitation preoperatively,” said Dr. Bolling. “Under anesthesia, four-plus TR can become mild.” Accordingly, any significant intraoperative TR or a dilated annulus should be considered indications for tricuspid valve repair, he said.
Though adding TV repair to mitral surgery may add some complexity, it does not necessarily add risk, said Dr. Bolling, citing a study of 110 matched patients with FTR that found a trend toward lower 30-day mortality for combined repair, when compared to mitral repair only (2% versus 8.5%, P = .2).
However, the single-intervention group had a 40% rate of tricuspid progression compared to 5% when both valves were repaired, and the 5-year survival rate was higher for those who had the combined surgery (74% versus 45%; Ann Thorac Surg. 2009 Mar;87[3]:698-703).
According to American College of Cardiology/American Heart Association (ACC/AHA) guidelines for managing valvular heart disease, which were last updated in 2014, patients with severe TR who are undergoing left-sided valve surgery should have concomitant TV repair, a class I recommendation.
The European Society of Cardiology and the European Association for Cardio-Thoracic Surgery (ESC/EACTS) 2012 guidelines are in accord with the ACC/AHA for this population, also issuing a class I recommendation.
For patients with greater than mild TR who have tricuspid annular dilation or right-sided heart failure, TV repair is a class IIa recommendation, according to the ACC/AHA guidelines. For patients with FTR who also have either pulmonary hypertension or right ventricular dilation or dysfunction, TV repair is an ACC/AHA class IIb recommendation.
In the European guidelines, patients with moderate secondary TR with a tricuspid annulus over 40 mm in diameter who are undergoing left-sided valve surgery, or who have right ventricular dilation or dysfunction, should undergo TV repair. This is a class IIa recommendation in the ESC/EACTS schema.
Dr. Bolling reported financial relationships with the Sorin Group, Medtronic, and Edwards Lifesciences.
[email protected]
On Twitter @karioakes
EXPERT ANALYSIS FROM HEART VALVE SUMMIT 2016
VIDEO: NAFLD costing U.S. $290 billion annually
BOSTON – A sophisticated mathematical analysis shows that nonalcoholic fatty liver disease is costing the United States over $290 billion annually. A similar economic burden was seen in several Western European countries as well.
The study, which incorporated available data about current cases of nonalcoholic fatty liver disease (NAFLD), looked at both medical and nonmedical costs, as the disease’s economic and social impact extends far beyond medical bills.
“It impacts patients’ quality of life, their work productivity; there’s a significant fatigue associated with that. In addition to this, there is an economic burden of nonalcoholic fatty liver disease,” said the study’s lead author, Zobair Younossi, MD, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Younossi, executive director of the Center for Liver Diseases at Inova Fairfax Hospital, Falls Church, Va., and his coinvestigators constructed a Markov chain to model costs associated with NAFLD. This mathematical technique allows the probability of the occurrence of an event to influence the model’s prediction of the probability of later events, a useful technique when trying to model real-world, dynamic conditions.
They used the Markov chain technique to model the transition of patients along the path of NAFLD progression. States included in the model were nonalcoholic steatohepatitis (NASH), NASH with fibrosis, compensated and decompensated cirrhosis, hepatocellular carcinoma, transplant, posttransplant, and death. The probabilities of progressing through these states were built from a meta-analysis and systematic literature review conducted by the authors, which they then adjusted by incorporating real-world data.
According to the model, annual direct medical costs are projected at $103 billion, or $1,613 for each of the 64 million NAFLD patients in the United States. The four European Union countries included in the model were Germany, France, Italy, and the United Kingdom. In aggregate, these countries are projected to have about 52 million people with NAFLD, for an annual cost of 35 billion euros. The estimated annual direct cost per patient varies by country, ranging from 354 euros to 1,163 euros.
When societal costs are incorporated, the numbers leap higher: to $292.19 billion in the United States, and over 200 billion euros in the four European countries studied.
In recent work, Dr. Younossi and his colleagues have reached an estimate that about a quarter of the world’s population has NAFLD. He said he was surprised to learn that the highest prevalences were in some areas of South America and the Middle East, with rapid increases in Asia as well.
However, the etiology of NAFLD helps explain these increases. “It’s really a phenotype. A number of different pathways lead to this disease; the most common is the one that is associated with obesity, type 2 diabetes, and insulin resistance,” said Dr. Younossi.
The subset of NAFLD patients who have NASH also risks progression to cirrhosis and hepatocellular carcinoma. According to Dr. Younossi’s examination of the UNOS transplant database, NASH is the second leading cause of liver transplantation in the United States, and one of the top three causes of death from liver disease.
These sobering data make the need for medical treatment for NASH an urgent priority, said Dr. Younossi. Currently, lifestyle modification such as weight loss is the only known treatment for NAFLD and NASH, “which is not easy to do,” he noted.
Several candidate drugs are in the pipeline currently. Also, said Dr. Younossi, NASH can be diagnosed only by liver biopsy currently, a risky and expensive procedure. The search is on for accurate and reliable imaging and serum biomarkers for NASH, so physicians can understand who’s most at risk for progression to more serious liver disease.
“The analysis quantifies the enormity of the clinical and economic burden of NAFLD, which will likely increase as incidence of NAFLD continues to rise with the increasing obesity and diabetes rates,” wrote Dr. Younossi and his coauthors.
Dr. Younossi reported having financial relationships with several pharmaceutical companies.
[email protected]
On Twitter @karioakes
BOSTON – A sophisticated mathematical analysis shows that nonalcoholic fatty liver disease is costing the United States over $290 billion annually. A similar economic burden was seen in several Western European countries as well.
The study, which incorporated available data about current cases of nonalcoholic fatty liver disease (NAFLD), looked at both medical and nonmedical costs, as the disease’s economic and social impact extends far beyond medical bills.
“It impacts patients’ quality of life, their work productivity; there’s a significant fatigue associated with that. In addition to this, there is an economic burden of nonalcoholic fatty liver disease,” said the study’s lead author, Zobair Younossi, MD, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Younossi, executive director of the Center for Liver Diseases at Inova Fairfax Hospital, Falls Church, Va., and his coinvestigators constructed a Markov chain to model costs associated with NAFLD. This mathematical technique allows the probability of the occurrence of an event to influence the model’s prediction of the probability of later events, a useful technique when trying to model real-world, dynamic conditions.
They used the Markov chain technique to model the transition of patients along the path of NAFLD progression. States included in the model were nonalcoholic steatohepatitis (NASH), NASH with fibrosis, compensated and decompensated cirrhosis, hepatocellular carcinoma, transplant, posttransplant, and death. The probabilities of progressing through these states were built from a meta-analysis and systematic literature review conducted by the authors, which they then adjusted by incorporating real-world data.
According to the model, annual direct medical costs are projected at $103 billion, or $1,613 for each of the 64 million NAFLD patients in the United States. The four European Union countries included in the model were Germany, France, Italy, and the United Kingdom. In aggregate, these countries are projected to have about 52 million people with NAFLD, for an annual cost of 35 billion euros. The estimated annual direct cost per patient varies by country, ranging from 354 euros to 1,163 euros.
When societal costs are incorporated, the numbers leap higher: to $292.19 billion in the United States, and over 200 billion euros in the four European countries studied.
In recent work, Dr. Younossi and his colleagues have reached an estimate that about a quarter of the world’s population has NAFLD. He said he was surprised to learn that the highest prevalences were in some areas of South America and the Middle East, with rapid increases in Asia as well.
However, the etiology of NAFLD helps explain these increases. “It’s really a phenotype. A number of different pathways lead to this disease; the most common is the one that is associated with obesity, type 2 diabetes, and insulin resistance,” said Dr. Younossi.
The subset of NAFLD patients who have NASH also risks progression to cirrhosis and hepatocellular carcinoma. According to Dr. Younossi’s examination of the UNOS transplant database, NASH is the second leading cause of liver transplantation in the United States, and one of the top three causes of death from liver disease.
These sobering data make the need for medical treatment for NASH an urgent priority, said Dr. Younossi. Currently, lifestyle modification such as weight loss is the only known treatment for NAFLD and NASH, “which is not easy to do,” he noted.
Several candidate drugs are in the pipeline currently. Also, said Dr. Younossi, NASH can be diagnosed only by liver biopsy currently, a risky and expensive procedure. The search is on for accurate and reliable imaging and serum biomarkers for NASH, so physicians can understand who’s most at risk for progression to more serious liver disease.
“The analysis quantifies the enormity of the clinical and economic burden of NAFLD, which will likely increase as incidence of NAFLD continues to rise with the increasing obesity and diabetes rates,” wrote Dr. Younossi and his coauthors.
Dr. Younossi reported having financial relationships with several pharmaceutical companies.
[email protected]
On Twitter @karioakes
BOSTON – A sophisticated mathematical analysis shows that nonalcoholic fatty liver disease is costing the United States over $290 billion annually. A similar economic burden was seen in several Western European countries as well.
The study, which incorporated available data about current cases of nonalcoholic fatty liver disease (NAFLD), looked at both medical and nonmedical costs, as the disease’s economic and social impact extends far beyond medical bills.
“It impacts patients’ quality of life, their work productivity; there’s a significant fatigue associated with that. In addition to this, there is an economic burden of nonalcoholic fatty liver disease,” said the study’s lead author, Zobair Younossi, MD, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Younossi, executive director of the Center for Liver Diseases at Inova Fairfax Hospital, Falls Church, Va., and his coinvestigators constructed a Markov chain to model costs associated with NAFLD. This mathematical technique allows the probability of the occurrence of an event to influence the model’s prediction of the probability of later events, a useful technique when trying to model real-world, dynamic conditions.
They used the Markov chain technique to model the transition of patients along the path of NAFLD progression. States included in the model were nonalcoholic steatohepatitis (NASH), NASH with fibrosis, compensated and decompensated cirrhosis, hepatocellular carcinoma, transplant, posttransplant, and death. The probabilities of progressing through these states were built from a meta-analysis and systematic literature review conducted by the authors, which they then adjusted by incorporating real-world data.
According to the model, annual direct medical costs are projected at $103 billion, or $1,613 for each of the 64 million NAFLD patients in the United States. The four European Union countries included in the model were Germany, France, Italy, and the United Kingdom. In aggregate, these countries are projected to have about 52 million people with NAFLD, for an annual cost of 35 billion euros. The estimated annual direct cost per patient varies by country, ranging from 354 euros to 1,163 euros.
When societal costs are incorporated, the numbers leap higher: to $292.19 billion in the United States, and over 200 billion euros in the four European countries studied.
In recent work, Dr. Younossi and his colleagues have reached an estimate that about a quarter of the world’s population has NAFLD. He said he was surprised to learn that the highest prevalences were in some areas of South America and the Middle East, with rapid increases in Asia as well.
However, the etiology of NAFLD helps explain these increases. “It’s really a phenotype. A number of different pathways lead to this disease; the most common is the one that is associated with obesity, type 2 diabetes, and insulin resistance,” said Dr. Younossi.
The subset of NAFLD patients who have NASH also risks progression to cirrhosis and hepatocellular carcinoma. According to Dr. Younossi’s examination of the UNOS transplant database, NASH is the second leading cause of liver transplantation in the United States, and one of the top three causes of death from liver disease.
These sobering data make the need for medical treatment for NASH an urgent priority, said Dr. Younossi. Currently, lifestyle modification such as weight loss is the only known treatment for NAFLD and NASH, “which is not easy to do,” he noted.
Several candidate drugs are in the pipeline currently. Also, said Dr. Younossi, NASH can be diagnosed only by liver biopsy currently, a risky and expensive procedure. The search is on for accurate and reliable imaging and serum biomarkers for NASH, so physicians can understand who’s most at risk for progression to more serious liver disease.
“The analysis quantifies the enormity of the clinical and economic burden of NAFLD, which will likely increase as incidence of NAFLD continues to rise with the increasing obesity and diabetes rates,” wrote Dr. Younossi and his coauthors.
Dr. Younossi reported having financial relationships with several pharmaceutical companies.
[email protected]
On Twitter @karioakes
Key clinical point:
Major finding: Annual direct medical costs alone are $1,613 for each of the estimated 64 million U.S. NAFLD patients.
Data source: Markov-chain modeling of NAFLD prevalence and morbidity in the United States and four European countries.
Disclosures: Dr. Younossi reported financial relationships with several pharmaceutical companies.
IV brivaracetam similarly well tolerated as oral formulation
HOUSTON – Pooled data for a recently approved antiepileptic drug show good safety and tolerability when it’s administered intravenously.
Intravenous brivaracetam, when given to 104 patients with epilepsy and 49 healthy volunteers, was generally well tolerated, though about one in three patients experienced somnolence, and one in four had some dizziness and fatigue. This adverse event profile was similar to that seen in clinical trials of the oral formulation of brivaracetam, Pavel Klein, MD, said in an interview during a poster session at the annual meeting of the American Epilepsy Society, though euphoria and dysgeusia were more common among healthy volunteers receiving intravenous brivaracetam.
“Looking at the side effects, the medication was well tolerated. … The main side effects were dizziness, somnolence, and fatigue, and by and large, these were mild or moderate. Nobody discontinued the medication because of side effects in the patient population,” said Dr. Klein, director of the Mid-Atlantic Epilepsy and Sleep Center, Bethesda, Md.
In the overall group of participants in all three studies, somnolence was seen in 30.1% of participants, dizziness in 15.7%, and fatigue in 15.0%. However, when compared with patients with epilepsy, healthy volunteers given brivaracetam 100 mg IV had a higher overall adverse event incidence, and notably more dizziness (35.5% versus 7.7%) and fatigue (29.0% versus 4.8%). One epilepsy patient in the phase III study (1/104; 1%) discontinued the study because of an adverse event.
Also, healthy volunteers, rather than patients, were more likely to experience euphoric mood and dysgeusia with intravenous as compared with oral brivaracetam.
The reason for these differences between the epilepsy and nonepilepsy groups is not known; however, wrote Dr. Klein and his coauthors, part of the difference might be “due to heterogeneous medical histories and concomitant medication use.”
Otherwise, intravenous brivaracetam administration was associated with about the same number of adverse events as when the drug was taken orally.
Brivaracetam, approved earlier in 2016, like levetiracetam, is a ligand for the synaptic vesicle protein 2a, the mechanism that’s thought to be responsible for the antiepileptic effect of this drug class. However, brivaracetam has a 15- to 30-fold higher affinity for its target than its older cousin. It’s approved in the United States as adjunctive therapy for focal seizures in individuals aged 16 and older with epilepsy. When administered intravenously, brivaracetam may be given as a bolus or an infusion over 15 minutes.
Dr. Klein serves on the speakers bureau of UCB Pharma, and has received research support from the company, which funded the study and assisted with poster preparation.
[email protected]
On Twitter @karioakes
HOUSTON – Pooled data for a recently approved antiepileptic drug show good safety and tolerability when it’s administered intravenously.
Intravenous brivaracetam, when given to 104 patients with epilepsy and 49 healthy volunteers, was generally well tolerated, though about one in three patients experienced somnolence, and one in four had some dizziness and fatigue. This adverse event profile was similar to that seen in clinical trials of the oral formulation of brivaracetam, Pavel Klein, MD, said in an interview during a poster session at the annual meeting of the American Epilepsy Society, though euphoria and dysgeusia were more common among healthy volunteers receiving intravenous brivaracetam.
“Looking at the side effects, the medication was well tolerated. … The main side effects were dizziness, somnolence, and fatigue, and by and large, these were mild or moderate. Nobody discontinued the medication because of side effects in the patient population,” said Dr. Klein, director of the Mid-Atlantic Epilepsy and Sleep Center, Bethesda, Md.
In the overall group of participants in all three studies, somnolence was seen in 30.1% of participants, dizziness in 15.7%, and fatigue in 15.0%. However, when compared with patients with epilepsy, healthy volunteers given brivaracetam 100 mg IV had a higher overall adverse event incidence, and notably more dizziness (35.5% versus 7.7%) and fatigue (29.0% versus 4.8%). One epilepsy patient in the phase III study (1/104; 1%) discontinued the study because of an adverse event.
Also, healthy volunteers, rather than patients, were more likely to experience euphoric mood and dysgeusia with intravenous as compared with oral brivaracetam.
The reason for these differences between the epilepsy and nonepilepsy groups is not known; however, wrote Dr. Klein and his coauthors, part of the difference might be “due to heterogeneous medical histories and concomitant medication use.”
Otherwise, intravenous brivaracetam administration was associated with about the same number of adverse events as when the drug was taken orally.
Brivaracetam, approved earlier in 2016, like levetiracetam, is a ligand for the synaptic vesicle protein 2a, the mechanism that’s thought to be responsible for the antiepileptic effect of this drug class. However, brivaracetam has a 15- to 30-fold higher affinity for its target than its older cousin. It’s approved in the United States as adjunctive therapy for focal seizures in individuals aged 16 and older with epilepsy. When administered intravenously, brivaracetam may be given as a bolus or an infusion over 15 minutes.
Dr. Klein serves on the speakers bureau of UCB Pharma, and has received research support from the company, which funded the study and assisted with poster preparation.
[email protected]
On Twitter @karioakes
HOUSTON – Pooled data for a recently approved antiepileptic drug show good safety and tolerability when it’s administered intravenously.
Intravenous brivaracetam, when given to 104 patients with epilepsy and 49 healthy volunteers, was generally well tolerated, though about one in three patients experienced somnolence, and one in four had some dizziness and fatigue. This adverse event profile was similar to that seen in clinical trials of the oral formulation of brivaracetam, Pavel Klein, MD, said in an interview during a poster session at the annual meeting of the American Epilepsy Society, though euphoria and dysgeusia were more common among healthy volunteers receiving intravenous brivaracetam.
“Looking at the side effects, the medication was well tolerated. … The main side effects were dizziness, somnolence, and fatigue, and by and large, these were mild or moderate. Nobody discontinued the medication because of side effects in the patient population,” said Dr. Klein, director of the Mid-Atlantic Epilepsy and Sleep Center, Bethesda, Md.
In the overall group of participants in all three studies, somnolence was seen in 30.1% of participants, dizziness in 15.7%, and fatigue in 15.0%. However, when compared with patients with epilepsy, healthy volunteers given brivaracetam 100 mg IV had a higher overall adverse event incidence, and notably more dizziness (35.5% versus 7.7%) and fatigue (29.0% versus 4.8%). One epilepsy patient in the phase III study (1/104; 1%) discontinued the study because of an adverse event.
Also, healthy volunteers, rather than patients, were more likely to experience euphoric mood and dysgeusia with intravenous as compared with oral brivaracetam.
The reason for these differences between the epilepsy and nonepilepsy groups is not known; however, wrote Dr. Klein and his coauthors, part of the difference might be “due to heterogeneous medical histories and concomitant medication use.”
Otherwise, intravenous brivaracetam administration was associated with about the same number of adverse events as when the drug was taken orally.
Brivaracetam, approved earlier in 2016, like levetiracetam, is a ligand for the synaptic vesicle protein 2a, the mechanism that’s thought to be responsible for the antiepileptic effect of this drug class. However, brivaracetam has a 15- to 30-fold higher affinity for its target than its older cousin. It’s approved in the United States as adjunctive therapy for focal seizures in individuals aged 16 and older with epilepsy. When administered intravenously, brivaracetam may be given as a bolus or an infusion over 15 minutes.
Dr. Klein serves on the speakers bureau of UCB Pharma, and has received research support from the company, which funded the study and assisted with poster preparation.
[email protected]
On Twitter @karioakes
AT AES 2016
Key clinical point:
Major finding: Somnolence was the most frequent adverse event with intravenous brivaracetam, reported by 30.1% of all study participants.
Data source: Pooled data from clinical trials in 104 patients with focal or generalized seizures and 49 healthy controls.
Disclosures: Dr. Klein serves on the speakers bureau of UCB Pharma, and has received research support from the company, which funded the study and assisted with poster preparation.
VIDEO: Angiogenesis has a role to play in NASH and NAFLD
BOSTON – A multimodal research process has provided clues to the role of angiogenesis in nonalcoholic fatty liver disease (NAFLD) and its more serious cousin, nonalcoholic steatohepatitis (NASH).
In constructing a protocol that began with patients, moved on to bioinformatics and then performed final validation in the petri dish, Savneet Kaur, PhD, and her colleagues were able to identify several angiogenesis genes likely to contribute to the development of NAFLD and NASH.
“We have seen angiogenic mechanisms and angiogenic genes in the pathophysiology of nonalcoholic fatty liver disease,” said Dr. Kaur, professor of biotechnology at Gautam Buddha Medical School, Greater Noida, India, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Kaur said that she and her coinvestigators began with a small group of eight patients with NASH, and seven patients with NAFLD, and also with seven healthy control participants. Genetic analysis and comparison of these patients yielded differential expression of certain genes already known to be associated with angiogenesis in the NASH and NAFLD, but not the healthy control participants.
“We did a microarray analysis, a high throughput gene expression study, and then we selected around 25 to 26 genes which were associated with oxidative stress and angiogenesis,” said Dr. Kaur.
For validation of these genes, Dr. Kaur and her associates used a larger study group of about 150 participants, again approximately evenly divided between those with mild NAFLD, those with more severe steatohepatitis, and healthy controls. “We validated the angiogenic genes in the subject group, and found that around 13 genes are preferentially expressed.”
“About 13 genes including VEGFR1, PIK3CA, CXCL8, NOS3, EREG, CCL2, PRKCE, PPar-gamma, PROK2, RUNX1, SIRT1, HMOX1 and CXCR4 showed significantly different gene expression in the [reverse transcription–polymerase chain reaction] analysis in Gr3 as compared to Gr1 (P less than .05 for each), whereas genes such as PIK3CA, CXCL8, NOS3, CCL2, PROK2, RUNX1, and HMOX1 were differentially expressed in Gr3 in comparison to Gr2 (P less than .05 each). A few genes, PPar-gamma, SIRT1, VEGFR1, HMOX1, PIK3CA, CXCR4, PROK2, and CCL2, showed correlations with fibrosis scores, angiogenesis scores, and NAFLD activity scores of the patients,” wrote Dr. Kaur and her colleagues in the abstract accompanying the poster presentation.
Taking these candidate genes, Dr. Kaur and her colleagues conducted a bioinformatics analysis to determine which transcription factors were controlling the genes. “We wanted to study the pathway – the mechanisms – to determine the upregulation and downregulation of these genes,” said Dr. Kaur.
Finally, Dr. Kaur and her associates took an in vitro approach, using human steatotic hepatocytes and endothelial cells, since “angiogenesis is a property of endothelial cells.” The two types of cells were cultured together, and angiogenic function and gene expression were examined, and checked against the genes and pathways identified in the first two steps. They again saw expression of the angiogenic pathways in the cell culture model. This was consistent with what is seen in patients with NAFLD and NASH: “Definitely, there’s an increase in angiogenesis. There’s an increase in the endothelial cell proliferation, with more fat, more steatosis in the patients,” said Dr. Kaur. Some genes, said Dr. Kaur, are “really important” to this process. Her group is now investigating how the genes are regulated, in order to understand better the precise role of angiogenesis in steatohepatitis.
The study was part of a joint Indo-German project, and sponsored by the Indian Council for Medical Research and the German Federal Ministry of Education and Research. Dr. Kaur reported no relevant conflicts of interest.
[email protected]
On Twitter @karioakes
BOSTON – A multimodal research process has provided clues to the role of angiogenesis in nonalcoholic fatty liver disease (NAFLD) and its more serious cousin, nonalcoholic steatohepatitis (NASH).
In constructing a protocol that began with patients, moved on to bioinformatics and then performed final validation in the petri dish, Savneet Kaur, PhD, and her colleagues were able to identify several angiogenesis genes likely to contribute to the development of NAFLD and NASH.
“We have seen angiogenic mechanisms and angiogenic genes in the pathophysiology of nonalcoholic fatty liver disease,” said Dr. Kaur, professor of biotechnology at Gautam Buddha Medical School, Greater Noida, India, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Kaur said that she and her coinvestigators began with a small group of eight patients with NASH, and seven patients with NAFLD, and also with seven healthy control participants. Genetic analysis and comparison of these patients yielded differential expression of certain genes already known to be associated with angiogenesis in the NASH and NAFLD, but not the healthy control participants.
“We did a microarray analysis, a high throughput gene expression study, and then we selected around 25 to 26 genes which were associated with oxidative stress and angiogenesis,” said Dr. Kaur.
For validation of these genes, Dr. Kaur and her associates used a larger study group of about 150 participants, again approximately evenly divided between those with mild NAFLD, those with more severe steatohepatitis, and healthy controls. “We validated the angiogenic genes in the subject group, and found that around 13 genes are preferentially expressed.”
“About 13 genes including VEGFR1, PIK3CA, CXCL8, NOS3, EREG, CCL2, PRKCE, PPar-gamma, PROK2, RUNX1, SIRT1, HMOX1 and CXCR4 showed significantly different gene expression in the [reverse transcription–polymerase chain reaction] analysis in Gr3 as compared to Gr1 (P less than .05 for each), whereas genes such as PIK3CA, CXCL8, NOS3, CCL2, PROK2, RUNX1, and HMOX1 were differentially expressed in Gr3 in comparison to Gr2 (P less than .05 each). A few genes, PPar-gamma, SIRT1, VEGFR1, HMOX1, PIK3CA, CXCR4, PROK2, and CCL2, showed correlations with fibrosis scores, angiogenesis scores, and NAFLD activity scores of the patients,” wrote Dr. Kaur and her colleagues in the abstract accompanying the poster presentation.
Taking these candidate genes, Dr. Kaur and her colleagues conducted a bioinformatics analysis to determine which transcription factors were controlling the genes. “We wanted to study the pathway – the mechanisms – to determine the upregulation and downregulation of these genes,” said Dr. Kaur.
Finally, Dr. Kaur and her associates took an in vitro approach, using human steatotic hepatocytes and endothelial cells, since “angiogenesis is a property of endothelial cells.” The two types of cells were cultured together, and angiogenic function and gene expression were examined, and checked against the genes and pathways identified in the first two steps. They again saw expression of the angiogenic pathways in the cell culture model. This was consistent with what is seen in patients with NAFLD and NASH: “Definitely, there’s an increase in angiogenesis. There’s an increase in the endothelial cell proliferation, with more fat, more steatosis in the patients,” said Dr. Kaur. Some genes, said Dr. Kaur, are “really important” to this process. Her group is now investigating how the genes are regulated, in order to understand better the precise role of angiogenesis in steatohepatitis.
The study was part of a joint Indo-German project, and sponsored by the Indian Council for Medical Research and the German Federal Ministry of Education and Research. Dr. Kaur reported no relevant conflicts of interest.
[email protected]
On Twitter @karioakes
BOSTON – A multimodal research process has provided clues to the role of angiogenesis in nonalcoholic fatty liver disease (NAFLD) and its more serious cousin, nonalcoholic steatohepatitis (NASH).
In constructing a protocol that began with patients, moved on to bioinformatics and then performed final validation in the petri dish, Savneet Kaur, PhD, and her colleagues were able to identify several angiogenesis genes likely to contribute to the development of NAFLD and NASH.
“We have seen angiogenic mechanisms and angiogenic genes in the pathophysiology of nonalcoholic fatty liver disease,” said Dr. Kaur, professor of biotechnology at Gautam Buddha Medical School, Greater Noida, India, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Dr. Kaur said that she and her coinvestigators began with a small group of eight patients with NASH, and seven patients with NAFLD, and also with seven healthy control participants. Genetic analysis and comparison of these patients yielded differential expression of certain genes already known to be associated with angiogenesis in the NASH and NAFLD, but not the healthy control participants.
“We did a microarray analysis, a high throughput gene expression study, and then we selected around 25 to 26 genes which were associated with oxidative stress and angiogenesis,” said Dr. Kaur.
For validation of these genes, Dr. Kaur and her associates used a larger study group of about 150 participants, again approximately evenly divided between those with mild NAFLD, those with more severe steatohepatitis, and healthy controls. “We validated the angiogenic genes in the subject group, and found that around 13 genes are preferentially expressed.”
“About 13 genes including VEGFR1, PIK3CA, CXCL8, NOS3, EREG, CCL2, PRKCE, PPar-gamma, PROK2, RUNX1, SIRT1, HMOX1 and CXCR4 showed significantly different gene expression in the [reverse transcription–polymerase chain reaction] analysis in Gr3 as compared to Gr1 (P less than .05 for each), whereas genes such as PIK3CA, CXCL8, NOS3, CCL2, PROK2, RUNX1, and HMOX1 were differentially expressed in Gr3 in comparison to Gr2 (P less than .05 each). A few genes, PPar-gamma, SIRT1, VEGFR1, HMOX1, PIK3CA, CXCR4, PROK2, and CCL2, showed correlations with fibrosis scores, angiogenesis scores, and NAFLD activity scores of the patients,” wrote Dr. Kaur and her colleagues in the abstract accompanying the poster presentation.
Taking these candidate genes, Dr. Kaur and her colleagues conducted a bioinformatics analysis to determine which transcription factors were controlling the genes. “We wanted to study the pathway – the mechanisms – to determine the upregulation and downregulation of these genes,” said Dr. Kaur.
Finally, Dr. Kaur and her associates took an in vitro approach, using human steatotic hepatocytes and endothelial cells, since “angiogenesis is a property of endothelial cells.” The two types of cells were cultured together, and angiogenic function and gene expression were examined, and checked against the genes and pathways identified in the first two steps. They again saw expression of the angiogenic pathways in the cell culture model. This was consistent with what is seen in patients with NAFLD and NASH: “Definitely, there’s an increase in angiogenesis. There’s an increase in the endothelial cell proliferation, with more fat, more steatosis in the patients,” said Dr. Kaur. Some genes, said Dr. Kaur, are “really important” to this process. Her group is now investigating how the genes are regulated, in order to understand better the precise role of angiogenesis in steatohepatitis.
The study was part of a joint Indo-German project, and sponsored by the Indian Council for Medical Research and the German Federal Ministry of Education and Research. Dr. Kaur reported no relevant conflicts of interest.
[email protected]
On Twitter @karioakes
AT THE LIVER MEETING 2016
Key clinical point:
Major finding: PPar-gamma, SIRT1, VEGFR1, and other genes are associated with fibrosis, angiogenesis, and steatosis.
Data source: Human bioinformatics–in vitro exploration of genetic pathways associated with angiogenesis in NASH and nonalcoholic fatty liver disease (NAFLD).
Disclosures: The study was part of a joint Indo-German project, and funded by the Indian Council for Medical Research and the German Federal Ministry of Education and Research. Dr. Kaur reported no relevant financial disclosures.
Sutureless aortic valve replacement: Is ease worth the cost?
CHICAGO – Rapid deployment sutureless valves can be a good option for some patients, providing a highly functional and nearly leakproof valve with less cardiopulmonary bypass and aortic cross-clamp times than those of conventional procedures.
“Why use a sutureless valve?” asked Vinod H. Thourani, MD, speaking at Heart Valve Summit 2016. He said that for many patients, there are abundant good reasons for the choice. The rapidity of the implantation procedure is a huge plus, he said. Cardiopulmonary bypass times are reduced when sutureless valve replacement is a stand-alone procedure, added Dr. Thourani, chief of cardiovascular surgery at Emory Hospital Midtown and codirector of the Structural Heart and Valve Center at Emory University, Atlanta. 
Rapid deployment is also of benefit in combined cases, or when patients have multiple comorbidities or poor left ventricular function. Sutureless valves, he said, are “optimal for multiple valve or concomitant procedures.”
Hemodynamics also are favorable, said Dr. Thourani; sutureless valves produce lower gradients than do their sutured alternatives, and work well in patients with a small aortic root.
Both sutureless valves that are currently available use bovine tissue; one, Sorin’s Perceval, uses a nitinol stent, while the Edwards’ Intuity uses stainless steel. The Perceval stent requires no sutures, while the Intuity requires just three. Also, the Perceval is collapsible, while the Intuity is not.
Removal of the pathologic valve in the sutureless procedure, he said, may contribute to the lower paravalvular leak and stroke rates than are seen in transcatheter aortic valve replacement (TAVR).
Expanded indications for sutureless valves include a calcified aortic root or a homograft; sutureless valves also can be used as an aortic valve redo, with patent grafts. Dr. Thourani said that he favors a transverse incision with a high aortotomy, about 2 cm above the sinotubular junction (STJ). In addition, off-label indications have included bicuspid aortic valve, pure aortic insufficiency, a prior mitral prosthesis or a degenerated aortic bioprosthesis, and a rescue procedure for a failed TAVR.
Dr. Thourani cited results of a trial conducted by Theodor Fischlein, MD, of Paracelsus Medical University in Nuremberg, Germany, and coauthors. These 1-year follow-up data from 628 patients participating in CAVALIER (Perceval S Valve Clinical Trial for Extended CE Mark), an international multicenter prospective trial, were presented at AATS 2016 (J Thorac Cardiovasc Surg. 2016 Jun;51[6]:1617-26.e4).
Of the 658 patients who met enrollment criteria and had a Perceval valve placement attempted, 30 wound up with a different prosthesis, most often because the correct valve size was not available. The remaining 628 patients who received the Perceval valve were included in the study. At 1 year, 549 patients remained; 50 had died, 12 had undergone valve explantation, and the remainder withdrew or were lost to follow-up.
Of the original Perceval recipients, 219 had received their valve via minimally invasive access. At 1 year, effective orifice area remained stable at the same mean 1.5 cm2 that was seen at discharge, an improvement from the mean 0.7 cm2 effective orifice area seen preoperatively. The mean pressure gradient, which was 45 mm Hg preoperatively, dropped precipitously to 10.3 mm Hg at discharge, and dropped a bit more at 1 year, to 9.2 mm Hg.
“This is a rapid and reproducible procedure: Over 20,000 implants have been performed worldwide,” said Dr. Thourani. The procedure looks good for low- to medium-risk patients, and may be the first procedure to consider for patients with a small aortic root, who have had prior coronary artery bypass surgery with patent grafts, or those with a calcified aortic root and homografts.
Questions still to be answered, he said, include whether “the cost will justify the decrease in cross-clamp times.” Also, though midrange results are good, longitudinal follow-up to track long-term valve hemodynamics is still ongoing.
Although patient demand seems to be high for a minimally invasive approach, sutureless valves still have low adoption rates, he said.
Dr. Thourani reported multiple financial relationships with medical device companies.
[email protected]
On Twitter @karioakes
CHICAGO – Rapid deployment sutureless valves can be a good option for some patients, providing a highly functional and nearly leakproof valve with less cardiopulmonary bypass and aortic cross-clamp times than those of conventional procedures.
“Why use a sutureless valve?” asked Vinod H. Thourani, MD, speaking at Heart Valve Summit 2016. He said that for many patients, there are abundant good reasons for the choice. The rapidity of the implantation procedure is a huge plus, he said. Cardiopulmonary bypass times are reduced when sutureless valve replacement is a stand-alone procedure, added Dr. Thourani, chief of cardiovascular surgery at Emory Hospital Midtown and codirector of the Structural Heart and Valve Center at Emory University, Atlanta.
Rapid deployment is also of benefit in combined cases, or when patients have multiple comorbidities or poor left ventricular function. Sutureless valves, he said, are “optimal for multiple valve or concomitant procedures.”
Hemodynamics also are favorable, said Dr. Thourani; sutureless valves produce lower gradients than do their sutured alternatives, and work well in patients with a small aortic root.
Both sutureless valves that are currently available use bovine tissue; one, Sorin’s Perceval, uses a nitinol stent, while the Edwards’ Intuity uses stainless steel. The Perceval stent requires no sutures, while the Intuity requires just three. Also, the Perceval is collapsible, while the Intuity is not.
Removal of the pathologic valve in the sutureless procedure, he said, may contribute to the lower paravalvular leak and stroke rates than are seen in transcatheter aortic valve replacement (TAVR).
Expanded indications for sutureless valves include a calcified aortic root or a homograft; sutureless valves also can be used as an aortic valve redo, with patent grafts. Dr. Thourani said that he favors a transverse incision with a high aortotomy, about 2 cm above the sinotubular junction (STJ). In addition, off-label indications have included bicuspid aortic valve, pure aortic insufficiency, a prior mitral prosthesis or a degenerated aortic bioprosthesis, and a rescue procedure for a failed TAVR.
Dr. Thourani cited results of a trial conducted by Theodor Fischlein, MD, of Paracelsus Medical University in Nuremberg, Germany, and coauthors. These 1-year follow-up data from 628 patients participating in CAVALIER (Perceval S Valve Clinical Trial for Extended CE Mark), an international multicenter prospective trial, were presented at AATS 2016 (J Thorac Cardiovasc Surg. 2016 Jun;51[6]:1617-26.e4).
Of the 658 patients who met enrollment criteria and had a Perceval valve placement attempted, 30 wound up with a different prosthesis, most often because the correct valve size was not available. The remaining 628 patients who received the Perceval valve were included in the study. At 1 year, 549 patients remained; 50 had died, 12 had undergone valve explantation, and the remainder withdrew or were lost to follow-up.
Of the original Perceval recipients, 219 had received their valve via minimally invasive access. At 1 year, effective orifice area remained stable at the same mean 1.5 cm2 that was seen at discharge, an improvement from the mean 0.7 cm2 effective orifice area seen preoperatively. The mean pressure gradient, which was 45 mm Hg preoperatively, dropped precipitously to 10.3 mm Hg at discharge, and dropped a bit more at 1 year, to 9.2 mm Hg.
“This is a rapid and reproducible procedure: Over 20,000 implants have been performed worldwide,” said Dr. Thourani. The procedure looks good for low- to medium-risk patients, and may be the first procedure to consider for patients with a small aortic root, who have had prior coronary artery bypass surgery with patent grafts, or those with a calcified aortic root and homografts.
Questions still to be answered, he said, include whether “the cost will justify the decrease in cross-clamp times.” Also, though midrange results are good, longitudinal follow-up to track long-term valve hemodynamics is still ongoing.
Although patient demand seems to be high for a minimally invasive approach, sutureless valves still have low adoption rates, he said.
Dr. Thourani reported multiple financial relationships with medical device companies.
[email protected]
On Twitter @karioakes
CHICAGO – Rapid deployment sutureless valves can be a good option for some patients, providing a highly functional and nearly leakproof valve with less cardiopulmonary bypass and aortic cross-clamp times than those of conventional procedures.
“Why use a sutureless valve?” asked Vinod H. Thourani, MD, speaking at Heart Valve Summit 2016. He said that for many patients, there are abundant good reasons for the choice. The rapidity of the implantation procedure is a huge plus, he said. Cardiopulmonary bypass times are reduced when sutureless valve replacement is a stand-alone procedure, added Dr. Thourani, chief of cardiovascular surgery at Emory Hospital Midtown and codirector of the Structural Heart and Valve Center at Emory University, Atlanta.
Rapid deployment is also of benefit in combined cases, or when patients have multiple comorbidities or poor left ventricular function. Sutureless valves, he said, are “optimal for multiple valve or concomitant procedures.”
Hemodynamics also are favorable, said Dr. Thourani; sutureless valves produce lower gradients than do their sutured alternatives, and work well in patients with a small aortic root.
Both sutureless valves that are currently available use bovine tissue; one, Sorin’s Perceval, uses a nitinol stent, while the Edwards’ Intuity uses stainless steel. The Perceval stent requires no sutures, while the Intuity requires just three. Also, the Perceval is collapsible, while the Intuity is not.
Removal of the pathologic valve in the sutureless procedure, he said, may contribute to the lower paravalvular leak and stroke rates than are seen in transcatheter aortic valve replacement (TAVR).
Expanded indications for sutureless valves include a calcified aortic root or a homograft; sutureless valves also can be used as an aortic valve redo, with patent grafts. Dr. Thourani said that he favors a transverse incision with a high aortotomy, about 2 cm above the sinotubular junction (STJ). In addition, off-label indications have included bicuspid aortic valve, pure aortic insufficiency, a prior mitral prosthesis or a degenerated aortic bioprosthesis, and a rescue procedure for a failed TAVR.
Dr. Thourani cited results of a trial conducted by Theodor Fischlein, MD, of Paracelsus Medical University in Nuremberg, Germany, and coauthors. These 1-year follow-up data from 628 patients participating in CAVALIER (Perceval S Valve Clinical Trial for Extended CE Mark), an international multicenter prospective trial, were presented at AATS 2016 (J Thorac Cardiovasc Surg. 2016 Jun;51[6]:1617-26.e4).
Of the 658 patients who met enrollment criteria and had a Perceval valve placement attempted, 30 wound up with a different prosthesis, most often because the correct valve size was not available. The remaining 628 patients who received the Perceval valve were included in the study. At 1 year, 549 patients remained; 50 had died, 12 had undergone valve explantation, and the remainder withdrew or were lost to follow-up.
Of the original Perceval recipients, 219 had received their valve via minimally invasive access. At 1 year, effective orifice area remained stable at the same mean 1.5 cm2 that was seen at discharge, an improvement from the mean 0.7 cm2 effective orifice area seen preoperatively. The mean pressure gradient, which was 45 mm Hg preoperatively, dropped precipitously to 10.3 mm Hg at discharge, and dropped a bit more at 1 year, to 9.2 mm Hg.
“This is a rapid and reproducible procedure: Over 20,000 implants have been performed worldwide,” said Dr. Thourani. The procedure looks good for low- to medium-risk patients, and may be the first procedure to consider for patients with a small aortic root, who have had prior coronary artery bypass surgery with patent grafts, or those with a calcified aortic root and homografts.
Questions still to be answered, he said, include whether “the cost will justify the decrease in cross-clamp times.” Also, though midrange results are good, longitudinal follow-up to track long-term valve hemodynamics is still ongoing.
Although patient demand seems to be high for a minimally invasive approach, sutureless valves still have low adoption rates, he said.
Dr. Thourani reported multiple financial relationships with medical device companies.
[email protected]
On Twitter @karioakes
EXPERT ANALYSIS FROM THE HEART VALVE SUMMIT 2016
